Lecture 2-Introduction to Immunology

Immune System

• Complex system of many biological strucutres and processes within an organism that protects against disease

• Directs a wide variety of pathogens

• Needs to distinguish pathogens from the organisms healthy tissue

Innate Immunity

• General protection

• Rapid

• non-specific

• No memory

• Early phase

Adaptive Immunity

• Antigen specific (B and T cells)

• Diverse

• Lag time between exposure and maximal response

• Produces with immunological memory

Types of Adaptive Immunity

• Humoral Immunity

• Cellular

Humoral Immunity

• Antibody-mediated

• B cells (Bone marrow)

Cellular Immunity

• Cell-mediated immunity

• T cells (Thymus)

Antigens

• Substances that produce and immune response

• composed of lipids, proteins, and carbohydrates

Epitopes

Antigenic sites

• Antigens can have multiple

Antibody

glycoproteins that bind antigens with high specificity

• immunoglobulin domains make up heavy and light chains

Antibody-Mediated Immunity

• B cells (lymphocytes) make and use an antibody as their specific antigen receptor

• The heavy chain region determines the antibody fate

Antibody Classes

• Different biological activities

• Deal with antigens with different protperties at different sites

IgA

• Found in mucous, saliva, tears, & breast milk

• Protects against pathogens that enter through mucosal surfaces

IgD

• Part of B cell receptor

• Activates basophils and mast cells

IgE

• Protects against parasitic worms

• Responsible for allergic reactions

IgG

• Secreted by plasma cells in the blood

• Crosses from the placenta into the fetus

• Protects against blood-borne virus infections

IgM

• Attached to surface of B cells or secreted into the blood

• Responsilbe for early stages of immunity

Lock & Key Antibody-Antigen Binding

highly specific, complementary binding between an antibody's paratope (lock) and an antigen's epitope (key)

Antibody (B cell receptor) Diversity

• created at the DNA level prior to antigen exposure

• Random gene rearrangement of exons

• Further diversity created by somatic mutations in V regions

Clonal Selection Theory of Antibody Formation

one B cell produces one antibody and then reproduces

Effector & Memory B cells

• Memory cells remain in greater numbers after infection clears

• gives rapid response on second exposure to an antigen

• basis to pathogen/vaccine induced immunity

Immunological Memory

• Low levels of antibody one week after first antigen exposure

• Second exposure produces faster response in a greater magnitude

Antibody Affinity

• Secondary response = faster and greater

• Comes from a mechanism that alters the variable regions of light and heavy chains of the memory cells by specific mutation

• Re-exposure to antigen is most likely to cause clonal expansion of memory cells which produce the highest affinity antibody.

Antiviral Activities of Antibodies

Antibodies trigger effector system that can lead to viral clearance

Antibody Dependent Cell-Mediated Cytotoxicity (ADCC)

an effector cell (natural killer cells, macrophages) actively lyses a virus-infected cell

Complement dependent cytotoxicity (CDC)

leads to virus-infected cell lysis

Virus Neutralization

Antibody can neutralize virus by tightly binding and blocking a critical biological activity resulting in loss of infectivity

T Helper Cells

regulate immune response by activating other immune cells

• B cells and other T cells

• Two types

Cytotoxic T Cells

Kill cells infected with intracellular pathogens

T cells

Protects against intracellular pathogens

B cells

Protect against extracellular pathogens

T Cell Mediated Immunity

Caused by direct action of T cells

Major Histocompatibility Complex (MHC)

evolved to present forigen antigens to T cells

MHC Class I

• Found on all nucleated cells

• NOT RBCs

MHC Class II

• Found on professional antigen presenting cells

• Ex: Dendritic cells, Macrophages, B cells, other specialized cells

MHC Diversity

• Based on anchor residues

• Do not vary for a specific MHC molecule —> only binds peptides with specigic anchor residues

Anchor Residues

Sites on peptides that bind MHC molecules

B-cell Receptor

T-cell Receptor

Has a specific antigen binding site (individual T cell specificity)

T-cell Receptor Diversity

• Stems from gene rearrangements during early T cell development

• Occurs randomly in the thymus

• Individual T cell specificity

Cytotoxic T cells Kills Infected Cell

1. Cytotoxic T cell binds to infected cell

2. Perforin makes holes in infected cell’s membrane and enzyme enters

3. Infected cell is destroyed

*Apoptosis better than necrosis

Th1

• Cell-mediated immunity dominates

• inflammatory immune response

Th2

• Humoral dominates

• Stimulating B cells and antibodies

Memory T cells

• Persist long after an infection is resolved

• Expand to large numbers of effector T cells upon re-exposure to antigen

Immunity Process

1. Selection of antigen specific t cells

2. proliferation, differentiation and development of effector cells of cellular immunity

3. Cell signalling and lymphokine production (Th, B, macrophages, other T cells)

4. Cytotoxic T cells eliminate virus infected cells